Novel Therapeutic Delivery Routes for the Management of PD OFF Episodes
Stuart Isaacson, MD: Let’s talk about this gap. You bring an interesting perspective on future directions for handling OFF episodes. Bob, you have participated in many programs. You mentioned earlier if we could have a twice-daily oral route, or if we could have a robust, well-tolerated transdermal route. Continuous infusions are examined. Where do you think this is heading? Do you think we need a new route of administration or a sophisticated long-acting oral drug? What do you think are the pathways if patients have been on a lot of these drug classes, as described by Raj? We have on-demand therapies, but we need to make sure they do it right. They do not want to undergo surgical treatments, either in the skull or in the abdomen. Where do you think this is heading?
Robert A. Hauser, MD, MBA: There will be ongoing efforts to find a very long-acting oral formulation of carbidopa-levodopa. There is a longer acting carbidopa-levodopa formulation in development called IPX203. The results have just been made public, which seems encouraging. It’s definitely not once or twice a day therapy. Most people might need it 3 or 4 times a day, but efforts will continue to be made to figure out how to get closer to a twice-daily oral. It looks very appealing to me. This is how most medications are administered. If a manufacturer could offer this, that would be ideal.
The other route that is getting a lot of attention is subcutaneous infusion. In development, there is a subcutaneous infusion of carbidopa-levodopa, plus another version of another manufacturer’s, as well as apomorphine for subcutaneous infusions. These will definitely hit the market. They have limitations related to a delivery system and the drugs themselves. They will try, as much as possible, to bridge the gap between our oral medications and device-assisted therapies or surgery.
Stuart Isaacson, MD: Raj, do you think these subcutaneous infusions will be additional advanced therapies? Or do you think they will fill an intermediate role somewhere between oral and surgical options?
Rajesh Pahwa, MD: They will bridge that gap between intermediate and surgical therapies with what we will eventually call these pump therapies. The only thing is that we cannot call them pump therapies because carbidopa-levodopa and enteral suspension are also given by pump. We have patients in whom we have tried complementary therapies and in whom we have given therapies on demand. Either they are not ready for surgery or their symptoms are not severe enough to require surgery, but they still have an OFF time. Even starting a subcutaneous levodopa infusion using subcutaneous apomorphine infusion can give them enough ON time without requiring brain stimulation or carbidopa-levodopa enteral suspension, all of which require two surgery to access this therapy. This is an unmet need that, in the near future, we could help our patients fill. I am very excited about this therapy, which will hopefully be available soon.
Transcript edited for clarity